Colon cancer is one of the most frequently diagnosed cancers in the United States. Poor prognosis also makes it one of the deadliest cancers. Dietary factors are closely associated with tumorigenesis and development of colon cancer. Soy foods and soy bioactive components have been linked to lower colon cancer incidence in populations consuming large quantity of soy foods. However there are controversies and mechanisms by which soy products and soy bioactive components exert anticancer effects remain unknown. Because of lack of scientific evidence on the mechanisms of soy foods'cancer prevention potentials, there are no nutritional recommendations regarding soy food consumption made to Americans. Based on current knowledge of colon cancer and preliminary data on beneficial actions of soy foods, the present proposal will test the hypothesis that dietary soy modulates colon cancer development through epigenetic mechanisms. A multi-generational exposure model will be used for epigenetic programming by soy foods in colon of offspring rats. Using techniques including electrospray ionization mass spectrometry, methylation analysis of CpG islands and chromatin immunoprecipitation coupled to a pathway-specific microarray, specific aims in this proposal include: 1) to survey epigenetic landscape of offspring after generations of soy feeding;2) to identify specific genes along the WNT signaling pathway that are modified epigenetically by generational soy diets;and 3) to monitor protection from getting colon cancer in later life of offspring rats after generational exposure to soy foods. Findings from this project will improve our understandings on anticancer mechanisms of soy products at epigenetic level and facilitate future experimental design for further research on soy foods and colon cancer prevention. Narrative of Relevance Findings from this project will improve our understandings on anticancer mechanisms of soy products at epigenetic level and aid future experimental design for further research on soy foods and colon cancer prevention. Data obtained will facilitate translational research in the future for using epigenetic signatures as molecular markers for early cancer detection.